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1.
Int Angiol ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32057213

RESUMO

BACKGROUND: Our knowledge on the burden of symptomatic and asymptomatic venous thromboembolism (VTE) in patients with cancer undergoing chemotherapy is limited. The aim of our study was to prospectively investigate the frequency of symptomatic VTE and asymptomatic deep vein thrombosis of the lower limbs among cancer patients undergoing chemotherapy. METHODS: We studied 231 patients (164 men) with pancreatic (n=36), lung (n=136), ovarian (n=32) or prostate (n=27) cancer receiving first line (n=192, 83.1%) or adjuvant chemotherapy, followed-up for 3-6 months. RESULTS: Some 17 patients were diagnosed with VTE, either asymptomatic detected on leg ultrasound (n=7) or symptomatic (n=10). The total frequency of VTE was 10.3% (17/165 with follow-up). Pancreatic cancer had the highest frequency of VTE (4/25, 16%) followed by ovarian (3/26, 11.5%) and lung cancer (10/94, 10.6%). There was no statistically significant difference in VTE rates among cancer types (p=0.36). VTE occurred more frequently in the presence of metastases (13/85, 15.3% vs. 4/80, 5.0%, for the remainder, p=0.03, OR 3.4). In the subgroup of patients receiving first line treatment, VTE occurred more frequently in patients with metastases (13/84, 15.5% vs 2/53, 3.8%, for the remainder, p=0.033). In patients with pancreatic, lung or ovarian cancer receiving first line treatment, VTE occurred more frequently in patients with metastatic disease (19.1% vs. 4.0%, for the remainder, p=0.015). CONCLUSIONS: VTE occurrence in this real-world patient cohort was high, reaching almost 20% in certain groups, like those with disseminated pancreatic, lung or ovarian cancer receiving first-line chemotherapy. Furthermore, VTE occurs mostly as a symptomatic event, being likely a result of the prothrombotic state of malignancy.

2.
Anticancer Res ; 40(1): 435-441, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892598

RESUMO

AIM: The purpose of the Imadje study was to confirm the efficacy and safety of imatinib, following resection of kit-positive gastrointestinal stromal tumour (GIST), in the adjuvant setting in the Greek population. PATIENTS AND METHODS: A total of 34 adult patients already receiving imatinib were enrolled. Recurrence-free (RFS) and overall survival, as well as time to treatment failure and safety were assessed. RESULTS: Overall survival could not be estimated in the present study, as no death occurred. Overall, 91.2% of patients were recurrence-free at 36 months, while the median time to treatment failure was 35 months. No new or unexpected safety findings were observed. Mutation analysis in 14 patients showed that the most frequent mutations were located in KIT exon 11 (64.3%) and exon 9 (28.6%). Univariate analysis showed that only surgical resection with a margin classification of R0 was associated with better RFS. CONCLUSION: Adjuvant treatment with imatinib for 3 years in patients with intermediate to high risk of recurrence was proven to prolong RFS, while being well-tolerated and not exhibiting a negative impact on patient compliance with therapy.


Assuntos
Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/patologia , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Grécia , Humanos , Mesilato de Imatinib/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Anticancer Res ; 40(1): 305-313, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892581

RESUMO

BACKGROUND: Cancer-associated thrombosis (CAT), the second leading cause of death in patients with cancer can be treated with low molecular weight heparin (LMWH) according to guidelines. PATIENTS AND METHODS: A multicenter prospective observational study was carried out to record anti-thrombotic treatment practice, assess thrombosis recurrence and bleeding, and identify potential risk factors. Adult patients from 18 Oncology Departments throughout Greece were followed-up for 12 months. RESULTS: A total of 120 patients with CAT receiving anticoagulant treatment were enrolled (35% incidental); 85% were treated for more than 6 months, 95.8% were treated with tinzaparin and smaller percentages with other agents. Thrombosis recurred in three patients and there was minor bleeding in four patients. Bleeding was associated with high body mass index (>35 kg/m2), trauma history, renal insufficiency and bevacizumab use. CONCLUSION: Incidental thrombosis contributes significantly to CAT burden. Long-term use of LMWH seems to be effective and safe. Several risk factors associated with bleeding should be considered during anti-coagulation therapy planning.


Assuntos
Neoplasias/complicações , Trombose/etiologia , Trombose/terapia , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Fatores de Risco
4.
J Am Acad Dermatol ; 82(2): 398-406, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31499156

RESUMO

BACKGROUND: In retrospective studies, a second primary melanoma (SPM) develops in 2%-20% of melanoma patients. Scarce evidence exists on the usefulness of total-body photography (TBP) and digital dermatoscopic documentation (DDD) for detecting SPMs. OBJECTIVE: The primary aim was to quantify the risk and investigate the time of occurrence of SPMs. Secondary aims were to identify risk factors for SPM and to assess the usefulness of TBP and DDD for SPM detection. METHODS: This prospective cohort included patients with recently diagnosed melanoma that underwent sequential clinical and dermatoscopic examinations for up to 5 years. Life table analysis and Kaplan-Meier survival analysis were performed. Multivariate Cox models were constructed to identify factors affecting the outcome. RESULTS: An SPM developed in 46 of 977 (4.7%) patients. Life table analysis revealed a 5-year cumulative risk of 8.0% for SPM. High nevus count, fair phototype, and occupational sun exposure were potent predictors of SPM. Of all new melanomas, 17.3% were diagnosed by clinical and dermatoscopic examination, 48.1% by TBP, and 34.6% by DDD. LIMITATIONS: All patients followed the same protocol and diagnostic bias associated with sequential dermatoscopic imaging. CONCLUSION: In this cohort, melanoma patients were at 8% risk of an SPM developing within 5 years. TBP and DDD significantly contributed to the early detection of SPM.

5.
J Med Genet ; 57(1): 53-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31300551

RESUMO

BACKGROUND: Gene panel testing has become the norm for assessing breast cancer (BC) susceptibility, but actual cancer risks conferred by genes included in panels are not established. Contrarily, deciphering the missing hereditability on BC, through identification of novel candidates, remains a challenge. We aimed to investigate the mutation prevalence and spectra in a highly selected cohort of Greek patients with BC, questioning an extensive number of genes, implicated in cancer predisposition and DNA repair, while calculating gene-specific BC risks that can ultimately lead to important associations. METHODS: To further discern BC susceptibility, a comprehensive 94-cancer gene panel was implemented in a cohort of 1382 Greek patients with BC, highly selected for strong family history and/or very young age (<35 years) at diagnosis, followed by BC risk calculation, based on a case-control analysis. RESULTS: Herein, 31.5% of patients tested carried pathogenic variants (PVs) in 28 known, suspected or candidate BC predisposition genes. In total, 24.8% of the patients carried BRCA1/2 loss-of-function variants. An additional 6.7% carried PVs in additional genes, the vast majority of which can be offered meaningful clinical changes. Significant association to BC predisposition was observed for ATM, PALB2, TP53, RAD51C and CHEK2 PVs. Primarily, compared with controls, RAD51C PVs and CHEK2 damaging missense variants were associated with high (ORs 6.19 (Exome Aggregation Consortium (ExAC)) and 12.6 (Fabulous Ladies Over Seventy (FLOSSIES)), p<0.01) and moderate BC risk (ORs 3.79 (ExAC) and 5.9 (FLOSSIES), p<0.01), respectively. CONCLUSION: Studying a large and unique cohort of highly selected patients with BC, deriving from a population with founder effects, provides important insight on distinct associations, pivotal for patient management.

6.
PLoS One ; 14(12): e0226853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860648

RESUMO

BACKGROUND: Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of "liquid biopsy" and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy. METHODS: Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms. RESULTS: At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p.T790M mutation, with NGS being able to detect this mutation in three 3 additional patients. CONCLUSIONS: This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice.

7.
Ann Gastroenterol ; 31(6): 698-704, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386120

RESUMO

Background: A phase I/II study to define the maximum tolerated dose (MTD) of biweekly docetaxel/cisplatin/5-fluorouracil (DCF) plus panitumumab (P), its efficacy, and tolerability as first-line treatment in advanced gastroesophageal cancer. Methods: In phase I part, patients with unresectable locally advanced or metastatic adenocarcinomas of the stomach or the gastroesophageal junction received cisplatin (40 mg/m2 on day 1), leucovorin (400 mg/m2 on day 1), 5-fluorouracil (400 mg/m2 bolus on day 1), 5-fluorouracil (1000 mg/m2/daycontinuous infusion on days 1-2), and escalated doses of docetaxel (on day 1) plus P (6 mg/kg on day 1) every 2 weeks. In phase II part, patients were treated with DCF/P at the MTD and the primary endpoint was response rate. The expected response rate was set at >40%. Results: The MTD for docetaxel in the mDCF/P was defined at 40 mg/m2 and a total of 40 evaluable patients were enrolled in phase II study. One (2.5%) complete and 13 (32.5%) partial responses (overall response rate: 35%), as well as 16 (40%) disease stabilizations were documented. The median progression-free survival was 6.9 months (95% confidence interval [CI] 3.5-10.3) and the median overall survival was 11.3 months (95%CI 7.7-14.8). Grade 3-4 neutropenia occurred in 10 patients (25%) and febrile neutropenia in 2 (5%). Allergic reactions (grade 1-4) occurred in 9 patients (22.5%). There was 1 treatment-related death. Conclusions: mDCF/P combination was feasible, though associated with a poor toxicity profile. However, the study failed to meet its primary endpoint and was terminated prematurely due to futility.

8.
N Engl J Med ; 378(13): 1177-1188, 2018 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-29590544

RESUMO

BACKGROUND: Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures. METHODS: We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12. RESULTS: After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority). CONCLUSIONS: Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Doenças do Sistema Nervoso/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
9.
Ann Gastroenterol ; 31(1): 65-70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29333068

RESUMO

Background: This study evaluated the safety and efficacy of nab-paclitaxel as second-line treatment in patients with advanced gastric adenocarcinoma. Methods: Thirty-nine pretreated patients [33 with taxane-based regimens (docetaxel, cisplatin, and fluorouracil)] and 6 with combination of fluoropyrimidines plus cisplatin with locally advanced inoperable and metastatic gastric and gastroesophageal junction adenocarcinoma were treated with weekly nab-paclitaxel (150 mg/m2 d1, d8, d15 in cycles of 28 days). Results: Partial response (PR) was documented in nine patients (23.1%; 95% confidence interval 10.1-37.2%), stable disease (SD) in 11 (28.2%) and disease progression in 18 (46.2%). The disease control rate (SD + PR + complete response) was 51.3%. Grade 3 and 4 neutropenia occurred in 10.2% and 5.1% of patients, respectively; grade 3 anemia in 5.1%; grade 3 neurotoxicity in 5.1%; and grade 2 pain in 5.1%. The median progression-free survival was 3.0 months (range 0.3-13.6) and the median overall survival 6.8 months (range 0.3-22). Conclusion: Nab-paclitaxel as second-line treatment in locally advanced inoperable or metastatic gastric and gastroesophageal junction carcinoma is an active chemotherapy regimen with a manageable toxicity profile and merits further evaluation.

10.
Oncol Rep ; 38(6): 3419-3429, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29130105

RESUMO

Non­small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues. Furthermore, the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel was used for fusion RNA transcript analysis. The mutation spectrum of the tumors was determined in a cohort of 502 patients with NSCLC using the aforementioned targeted gene panels. The panel used for tumor DNA analysis in this study exhibited high rates (100%) of sensitivity, specificity and reproducibility at a mutation allelic frequency of 3%. At least one DNA mutation was detected in 374 patients (74.5%) and an RNA fusion was identified in 16 patients, (3.2%). In total, alterations in a cancer-driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested. Among the NSCLC patients, 23% presented a mutation in a gene associated with approved or emerging targeted therapy. More specifically, 13.5% (68/502) presented a mutation in a gene with approved targeted therapy (EGFR, ALK, ROS1) and 9.4% (47/502) had an alteration in a gene related to emerging targeted therapies (ERBB2, BRAF, MET and RET). Furthermore, 51.6% of the patients had a mutation in a gene that could be related to an off label therapy or indicative for access to a clinical trial. Thus, the targeted NGS panel used in this study is a reliable approach for tumor molecular profiling and can be applied in personalized treatment decision making for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Mutação , Análise de Sequência de DNA/métodos , Feminino , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Masculino , Terapia de Alvo Molecular
11.
Br J Cancer ; 117(2): 164-170, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28641315

RESUMO

BACKGROUND: Sequential anthracyclines and taxanes are standard adjuvant chemotherapy for patients with high-risk axillary node-positive breast cancer. We compared a sequential to a concurrent regimen in high-risk node-negative early breast cancer. METHODS: Patients were eligible if they had tumours >2 cm or T1c with two of the following characteristics: no oestrogen receptor (ER) and progesterone receptor (PR) expression, histological grade III, Ki67 >40% and vascular, lymphovascular or perineural invasion. They were randomised to receive four cycles of epirubicin 90 mg m-2 followed by four cycles of docetaxel 75 mg m-2 (sequential regimen) or six cycles of epirubicin 75 mg m-2 plus docetaxel 75 mg m-2 (concurrent regimen). All chemotherapy cycles were administered every 21 days with G-CSF prophylaxis only for the concurrent arm. The primary endpoint was disease-free survival (DFS). RESULTS: Between 2001 and 2013, 658 women received the sequential (n=329) or the concurrent (n=329) regimen. The median age was 53 years, 43.9% of the patients were premenopausal and of the tumours 44.2% were ⩽2 cm, 52.7% histological grade 3 and 35.3% hormone receptor-negative. After a median follow-up of 70.5 months, there were 29 (8.8%) vs 42 (12.8%) disease relapses (P=0.102) and 11 (3.3%) vs 19 (5.8%) deaths (P=0.135), in the sequential and concurrent arm, respectively. The 5-year DFS rates were 92.6% vs 88.2% for sequential and concurrent arm, respectively (hazard ratio (HR): 1.591; 95% confidence interval (CI): 0.990-2.556; P=0.055). Toxicity included grade 2-4 neutropenia in 54% vs 41% (P=0.001), febrile neutropenia 2.7% vs 6.1% (P=0.06), nausea/vomiting 18.5% vs 12.4% (P=0.03) of patients in the sequential and concurrent arm. There were no toxic deaths. CONCLUSIONS: Sequential compared with the concurrent administration of anthracyclines and taxanes is associated with a non-significant but possibly clinically meaningful improvement in DFS. In the era of molecular selection of patients for adjuvant chemotherapy, this study offers valuable information for the optimal administration of anthracyclines and taxanes in patients with node-negative disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Epirubicina/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias
12.
Ann Gastroenterol ; 29(4): 390-416, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27708505

RESUMO

There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.

13.
Ann Gastroenterol ; 29(2): 103-26, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27064746

RESUMO

In rectal cancer management, accurate staging by magnetic resonance imaging, neo-adjuvant treatment with the use of radiotherapy, and total mesorectal excision have resulted in remarkable improvement in the oncological outcomes. However, there is substantial discrepancy in the therapeutic approach and failure to adhere to international guidelines among different Greek-Cypriot hospitals. The present guidelines aim to aid the multidisciplinary management of rectal cancer, considering both the local special characteristics of our healthcare system and the international relevant agreements (ESMO, EURECCA). Following background discussion and online communication sessions for feedback among the members of an executive team, a consensus rectal cancer management was obtained. Statements were subjected to the Delphi methodology voting system on two rounds to achieve further consensus by invited multidisciplinary international experts on colorectal cancer. Statements were considered of high, moderate or low consensus if they were voted by ≥80%, 60-80%, or <60%, respectively; those obtaining a low consensus level after both voting rounds were rejected. One hundred and two statements were developed and voted by 100 experts. The mean rate of abstention per statement was 12.5% (range: 2-45%). In the end of the process, all statements achieved a high consensus. Guidelines and algorithms of diagnosis and treatment were proposed. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized.

14.
Ann Gastroenterol ; 29(1): 3-17, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26752945

RESUMO

Despite considerable improvement in the management of colon cancer, there is a great deal of variation in the outcomes among European countries, and in particular among different hospital centers in Greece and Cyprus. Discrepancy in the approach strategies and lack of adherence to guidelines for the management of colon cancer may explain the situation. The aim was to elaborate a consensus on the multidisciplinary management of colon cancer, based on European guidelines (ESMO and EURECCA), and also taking into account local special characteristics of our healthcare system. Following discussion and online communication among members of an executive team, a consensus was developed. Statements entered the Delphi voting system on two rounds to achieve consensus by multidisciplinary international experts. Statements with an agreement rate of ≥80% achieved a large consensus, while those with an agreement rate of 60-80% a moderate consensus. Statements achieving an agreement of <60% after both rounds were rejected and not presented. Sixty statements on the management of colon cancer were subjected to the Delphi methodology. Voting experts were 109. The median rate of abstain per statement was 10% (range: 0-41%). In the end of the voting process, all statements achieved a consensus by more than 80% of the experts. A consensus on the management of colon cancer was developed by applying the Delphi methodology. Guidelines are proposed along with algorithms of diagnosis and treatment. The importance of centralization, care by a multidisciplinary team, and adherence to guidelines is emphasized.

15.
Ann Gastroenterol ; 29(1): 18-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26751386

RESUMO

Colorectal cancer remains a major cause of cancer mortality in the Western world both in men and women. In this manuscript a concise overview and recommendations on adjuvant chemotherapy in colon cancer are presented. An executive team from the Hellenic Society of Medical Oncology was assigned to develop a consensus statement and guidelines on the adjuvant treatment of colon cancer. Fourteen statements on adjuvant treatment were subjected to the Delphi methodology. Voting experts were 68. All statements achieved a rate of consensus above than 80% (>87%) and none revised and entered to a second round of voting. Three and 8 of them achieved a 100 and an over than 90% consensus, respectively. These statements describe evaluations of therapies in clinical practice. They could be considered as general guidelines based on best available evidence for assistance in treatment decision-making. Furthermore, they serve to identify questions and targets for further research and the settings in which investigational therapy could be considered.

16.
Biomark Cancer ; 7(Suppl 1): 1-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26056505

RESUMO

Gastrointestinal stromal tumors (GIST) are the most common sarcomas of the gastrointestinal tract, with transformation typically driven by activating mutations of cKIT and less commonly platelet-derived growth factor receptor alpha (PDGFRA). Successful targeting of tyrosine-protein kinase Kit with imatinib, a tyrosine kinase inhibitor, has had a major impact in the survival of patients with GIST in both the adjuvant and metastatic setting. A recent modification of treatment guidelines for patients with localized, high-risk GIST extended the adjuvant treatment duration from 1 year to 3 years. In this paper, we review the clinical data of patients with GIST treated in the Oncology Outpatient Unit of "Attikon" University Hospital and aim to assess which patients are eligible for prolongation of adjuvant imatinib therapy as currently suggested by treatment recommendations.

17.
Am J Clin Oncol ; 38(1): 17-22, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23563209

RESUMO

INTRODUCTION: We conducted a feasibility study on docetaxel/capecitabine/cisplatin (DCX) with chemoradiotherapy as adjuvant treatment for gastric cancer patients. METHODS: Patients were scheduled to receive 2 cycles of DCX, followed by 50.4 Gy plus capecitabine as radiotherapy, followed by an additional 2-DCX cycles. RESULTS: From the 40 enrolled patients, 26 (65%) completed treatment as per protocol and 14 (35%) discontinued with the treatment (patients' refusal: n=6; adverse events: n=8). There were 2 toxic deaths. Grade >3 toxicity was 12.1% before and 13.3% after chemoradiotherapy. Disease progression was documented in 11 (27.5%) patients. CONCLUSIONS: No further development of this regimen is justified on the basis of poor tolerability in patients.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia , Neoplasias Gástricas/terapia , Adulto , Idoso , Anemia/induzido quimicamente , Capecitabina , Quimiorradioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Parada Cardíaca/induzido quimicamente , Humanos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Sepse/etiologia , Taxoides/administração & dosagem , Resultado do Tratamento
18.
Breast Cancer Res Treat ; 148(3): 591-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25399229

RESUMO

Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive early breast cancer. However, which is the preferable taxane in a dose-dense regimen remains unknown. We conducted a randomized study to compare the efficacy of dose-dense paclitaxel versus docetaxel following 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) as adjuvant chemotherapy in women with node-positive early breast cancer. Following surgery women with HER2-negative breast cancer and at least one infiltrated axillary lymph node were randomized to receive four cycles of FEC (700/75/700 mg/m(2)) followed by four cycles of either paclitaxel (175 mg/m(2)) or docetaxel (75 mg/m(2)). All cycles were administered every 14 days with G-CSF support. The primary endpoint was disease-free survival (DFS) at 3 years. Between 2004 and 2007, 481 women were randomized to paclitaxel (n = 241) and docetaxel (n = 240). After a median follow-up of 6 years, 51 (21%) and 48 (20%) women experienced disease relapse (p = 0.753) and there was no significant difference in DFS between the paclitaxel- and docetaxel-treated groups (3-year DFS 87.4 vs. 88.3%, respectively; median DFS not reached; p = 0.633). Toxicities were manageable, with grade 2-4 neutropenia in 21 versus 31% (p = 0.01), thrombocytopenia 0.8 versus 3.4% (p = 0.06), any grade neurotoxicity 17 versus 7.5% (p = 0.35) and onycholysis 4.9 versus 12.1% (p = 0.03) for patients receiving paclitaxel and docetaxel, respectively. There were no toxic deaths. Dose-dense paclitaxel versus docetaxel after FEC as adjuvant chemotherapy results in a similar 3-year DFS rate in women with axillary node-positive early breast cancer. Due to its more favorable toxicity profile, paclitaxel is the taxane of choice in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Taxoides/efeitos adversos , Resultado do Tratamento
19.
PLoS One ; 9(11): e111612, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25372488

RESUMO

The EGF-induced MAP kinase cascade is one of the most important and best characterized networks in intracellular signalling. It has a vital role in the development and maturation of living organisms. However, when deregulated, it is involved in the onset of a number of diseases. Based on a computational model describing a "surface" and an "internalized" parallel route, we use systems biology techniques to characterize aspects of the network's functional organization. We examine the re-organization of protein groups from low to high external stimulation, define functional groups of proteins within the network, determine the parameter best encoding for input intensity and predict the effect of protein removal to the system's output response. Extensive functional re-organization of proteins is observed in the lower end of stimulus concentrations. As we move to higher concentrations the variability is less pronounced. 6 functional groups have emerged from a consensus clustering approach, reflecting different dynamical aspects of the network. Mutual information investigation revealed that the maximum activation rate of the two output proteins best encodes for stimulus intensity. Removal of each protein of the network resulted in a range of graded effects, from complete silencing to intense activation. Our results provide a new "vista" of the EGF-induced MAP kinase cascade, from the perspective of complex self-organizing systems. Functional grouping of the proteins reveals an organizational scheme contrasting the current understanding of modular topology. The six identified groups may provide the means to experimentally follow the dynamics of this complex network. Also, the vulnerability analysis approach may be used for the development of novel therapeutic targets in the context of personalized medicine.


Assuntos
Fator de Crescimento Epidérmico/metabolismo , Sistema de Sinalização das MAP Quinases , Modelos Biológicos , Algoritmos , Análise por Conglomerados , Fator de Crescimento Epidérmico/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ligação Proteica , Mapas de Interação de Proteínas
20.
Anticancer Res ; 34(10): 5649-55, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25275069

RESUMO

AIM: To determine the more effective dosing sequence of intermittent erlotinib and docetaxel for treating chemotherapy-naive patients with advanced Non-Small Cell Lung Cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized to receive daily erlotinib for 12 consecutive days prior to docetaxel (Arm A) or after docetaxel (Arm B). Progression-free survival (PFS) was the primary end-point; secondary end-points were overall survival (OS) and objective response rate (ORR). RESULTS: Fifty eligible patients received a total of 226 treatment cycles (median: 3). Median PFS and OS were 3.6 months and 10.5 months, respectively (differences were not statistically significant between the two arms). Neutropenia grade 3 and 4 occurred in 15 patients, while two patients developed grade 3 diarrhea. There were two treatment-related deaths (pulmonary embolism and non-neutropenic sepsis). CONCLUSION: Intermittent administration of erlotinib does not appear to improve the clinical outcome of single-agent docetaxel chemotherapy in unselected patients with NSCLC in the first-line setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Docetaxel , Cloridrato de Erlotinib , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Quinazolinas/administração & dosagem , Fatores de Risco , Taxoides/administração & dosagem , Resultado do Tratamento
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